FIELD OF THE INVENTION
This invention is directed to new organic compounds, and more particularly to 9H-dibenzoimidazo compounds, intermediates therefor and a process of production thereof.
The novel compounds, intermediates and processes of production thereof can be illustratively represented by the following schemes of formulae: ##SPC3##
Wherein R.sub.3 ' and R.sub.4 ' are hydrogen or alkyl of 1 to 3 carbon atoms, inclusive, and wherein R.sub.2 and R.sub.6 are hydrogen, halogen, or -CF.sub.3.
Compound III can be further modified as shown by Scheme B: ##SPC4##
wherein X" is bromine or chlorine, wherein R'.sub.1 is alkyl of 1 to 3 carbon atoms, inclusive, ##SPC5##
In which W is H, chlorine, or fluorine, or R.sub.1 is ##EQU5## IN WHICH N IS AN INTEGER OF 2 TO 4 AND R.sub.0 ' and R.sub.0 " are hydrogen and alkyl, defined as above, or together ##EQU6## PYRROLIDINO, PIPERIDINO, MORPHOLINO, OR N-methylpiperazino, and R.sub.2 and R.sub.6 are defined as in Scheme A, above.
Hydrolysis of those compounds of formula IIIA in which R.sub.1 is: ##SPC6##
In which W is defined as above, provides compounds of formula IIIB: ##SPC7##
in which R.sub.2, R.sub.3 ', R.sub.4 ', R.sub.6, and W are defined as herein above.
Compounds of formula III wherein R.sub.1 is methyl can also be obtained by the methods of Scheme C. ##SPC8##
wherein R.sub.2 and R.sub.6 are defined as herein above. If an alkyl group is in compound III, compounds such as III D and III E can be produced: ##SPC9## ##SPC10##
For Schemes D and E, R.sub.2 and R.sub.6 are defined as herein above, and Alkyl of 1 to 3 carbon atoms, inclusive.
A compound of formula III wherein R.sub.3 ' is alkyl and R.sub.4 ' is hydrogen can be converted with formaldehyde and a secondary amino compound ##EQU7## in which ##EQU8## is as described herein above, in monoglyme and in the presence of hydrochloric acid, into a compound of formula IIIF: ##SPC11##
wherein R.sub.2 and R.sub.6 and alkyl are defined as herein before and wherein ##EQU9## is pyrrolidino, piperidino, morpholino, N-methylpiperazino or dimethylamino.
In the same manner, compound IIIG: ##SPC12##
wherein R.sub.2, R.sub.6, Alkyl and ##EQU10## are defined as above, is prepared from compound III, wherein R.sub.4 ' is alkyl and R'.sub.3 is hydrogen.
The compounds of this invention can therefore be represented by the formula IIIH: ##SPC13##
wherein R.sub.1 is selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, ##SPC14##
or R.sub.1 is ##EQU11## in which n is an integer of 2 to 4, and R.sub.0 ' and R.sub.0 " are hydrogen or alkyl defined as above or, together ##EQU12## is pyrrolidino, piperidino, N-methylpiperazino, and morpholino; wherein R.sub.3 and R.sub.4 are hydrogen or alkyl as defined above, or, R.sub.3 and R.sub.4 can be ##EQU13## in which ##EQU14## is defined as above; and wherein R.sub.2 and R.sub.6 are selected from the group consisting of hydrogen, halogen, or CF.sub.3, and the pharmacologically acceptable acid addition salts thereof.
The more preferred compounds are those of formula III(I) ##SPC15##
wherein R".sub.1 is alkyl or ##EQU15## in which n is 2 to 4 and alkyl is in each of 1 to 3 carbon atoms, inclusive, and the pharmacologically acceptable acid addition salts thereof.
Other preferred compounds include those of the formula IIIJ. ##SPC16##
wherein R.sub.1 '" is hydrogen or alkyl of 1 to 3 carbon atoms, inclusive, and wherein R".sub.3 and R".sub.4 are hydrogen or alkyl as defined above, or R".sub.3 or R".sub.4 can be ##EQU16## in which R.sub.0 ' and R.sub.0 " are hydrogen or alkyl as defined above, or together ##EQU17## is pyrrolidino, piperidino, N-methylpiperazino, or morpholino, and the pharmacologically acceptable acid addition salts thereof.
The method of scheme A comprises treating a compound of formula 1 with a compound of formula ##EQU18## wherein R.sub.3 ' and R.sub.4 ' are hydrogen or alkyl of 1 to 3 carbon atoms, inclusive, to give compound II; and treating II with sulfuric acid to obtain a compound of the formula III.
The method of Scheme B comprises: Treating a compound of structure III with a strong base, e.g. sodium hydride, and then with a chloride or bromide of the formula RX" wherein R is alkyl of 1 to 3 carbon atoms, inclusive, ##SPC17##
in which W is hydrogen, chlorine, or fluorine, or R is ##EQU19## in which n is an integer of 2 to 4, and R.sub.0 ' and R.sub.0 " are hydrogen, or alkyl defined as above, or together ##EQU20## is pyrrolidino, piperidino, morpholino, or N-methyl-piperazino, and wherein X" is chlorine or bromine, to give the compound IIIA.
Hydrolysis of those compounds of formula IIIA in which R.sub.1 is ##SPC18##
defined as above gives the corresponding keto compound.
In the method of schemes C, D, and E a compound of formula III is treated with formaldehyde in formic acid to give a product IIIC or if already methylated in the 2- or 3-position to give a 2- or 3-hydroxymethyl derivative of the compound III, which may additionally be methylated in the 9-position (such as compouns IIIE).
The 2- or 3-hydroxymethyl compounds, IIID or IIIE, can be further treated with triethylamine and methanesulfonyl chloride followed by a secondary amine such as morpholine, pyrrolidine, piperidine, or N-methylpiperazine, to convert the alcoholic group to the corresponding amino group such as seen in compounds IIIF and IIIG.
Compounds IIIF and IIIG can also be directly obtained from a compound of formula III in which R.sub.3 ' or R.sub.4 ' is alkyl, by direct reaction of a compound of formula III with formaline, hydrochloric acid and a selected base such as pyrrolidine, piperidine, morpholine, N-methylpiperazine, or dimethylamine, in monoglyme at elevated temperatures.